The extracellular adenosine receptor has a modulatory role in the nervous, circulatory, endocrine, and immunological systems. The prospect of harnessing these effects specifically for therapeutic purposes is attractive. A functionalized congener approach to drug design in which a "carrier" molecule is attached to a receptor pharmacophore has been applied to the adenosine receptor to produce analogs of agonists and antagonists which have promise as therapeutic agents and as receptor probes. Prodrugs of adenosine agonists and antagonist targeted for the brain and kidneys are being designed. In the antagonist series new analogs which combine potency, water solubility, and A1-adenosine receptor selectivity in the same compound are now being evaluated in in vivo testing. In the central nervous system adenosine agonists act as cerebroprotective agents. We are developing new agonists as potential agents for treating stroke. Purine functionalized congeners are also being developed as adenosine receptor probes. An iodinated adenosine derivative, selective for the A2 subtype, was used to characterize the carbohydrate groups that are attached to the native receptor. Rabbit brain A2-receptors undergo a specific proteolysis that alters pharmacological properties.